A close look at Günter Blobel’s transformative contributions to molecular cell biology. The difficulty of reconciling chemical mechanisms with the functions of whole living systems has plagued biologists since the development of cell theory in the nineteenth century.As Karl S. Matlin argues in Crossing the Boundaries of Life, it is no coincidence that this longstanding knot of scientific inquiry was loosened most meaningfully by the work of a cell biologist, the Nobel laureate Günter Blobel. In 1975, using an experimental setup that did not contain any cells at all, Blobel was able to target newly made proteins to cell membrane vesicles, enabling him to theorize how proteins in the cell distribute spatially, an idea he called the signal hypothesis.Over the next twenty years, Blobel and other scientists were able to dissect this mechanism into its precise molecular details. For elaborating his signal concept into a process he termed membrane topogenesis—the idea that each protein